Laminin, a glycoprotein of basement membranes, binds to a specific receptor on the surface of neoplastic and non-neoplastic cells. Laminin exhibits saturatable and competible binding to the surface of cultured living cells, or to isolated plasma membranes from cells or tissue. The binding coefficient is 2 nM with 50,000 receptors per cell. The receptor was isolated from murine and human carcinomas and melanomas. It has a molecular weight of approximately 67,000 daltons. The laminin receptor purified from human breast carcinoma plasma membranes was used as an antigen to generate monoclonal antibodies (mAbs). Using immunoblotting, the mAbs recognize a single about 67,000 dalton protein among all the proteins extracted from breast carcinoma plasma membranes. The mAbs differed in their ability to block binding of laminin to the plasma membrane receptor. Antibody LR1 inhibited virtually 100% of the specific binding of laminin to both the isolated human breast - carcinoma plasma membranes or the living MCF-7 cells. In contrast, antibody LR2 had no effect on laminin binding under identical conditions. Thus, the two types of mAbs may recognize different functional domains on the laminin receptor. Preincubation of metastatic murine melanoma cells with syngeneic whole laminin followed by tail vein injection increased tumor cell retention in the lung and strongly stimulated metastases formation. The domain of the laminin molecule responsible for stimulating metastases was identified. Laminin in a cross-shaped molecule with three short arms and one long arm. All arms have globular end regions. Purified protease-derived fragments of laminin were prepared which a) lacked only the long arm of the molecule (alpha fragment), or b) lacked both the long arm and the globular end regions of the short arms (C1 fragment). Both types of fragments contained the laminin receptor binding region. The fragments had opposite effects on metastases. The alpha fragment stimulated metastases formation to the same extent as whole laminin. In contrast, the C1 fragment inhibited or abolished metastases formation.